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Effects of sustained antiangiogenic therapy in multistage prostate cancer in TRAMP model
- Source :
- Cancer research. 67(12)
- Publication Year :
- 2007
-
Abstract
- Antiangiogenic therapy is a promising alternative for prostate cancer growth and metastasis and holds great promise as an adjuvant therapy. The present study evaluated the potential of stable expression of angiostatin and endostatin before the onset of neoplasia and during the early and late stages of prostate cancer progression in transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Groups of 5-, 10-, and 18-week-old male TRAMP mice received recombinant adeno-associated virus-6 encoding mouse endostatin plus angiostatin (E+A) by i.m. injection. The effects of therapy were determined by sacrificing groups of treated mice at defined stages of tumor progression and following cohorts of similarly treated mice for long-term survival. Results indicated remarkable survival after recombinant adeno-associated virus–(E+A) therapy only when the treatment was given at an earlier time, before the onset of high-grade neoplasia, compared with treatment given for invasive cancer. Interestingly, early-stage antiangiogenic therapy arrested the progression of moderately differentiated carcinoma to poorly differentiated state and distant metastasis. Immunohistochemical analysis of the prostate from treated mice indicated significantly lower endothelial cell proliferation and increased tumor cell apoptosis. Vascular endothelial growth factor receptor (VEGFR)-2 expression was significantly down-regulated in tumor endothelium after treatment but not VEGFR-1. Analysis of the neuroendocrine marker synaptophysin expression indicated that antiangiogenic therapy given at an early-stage disease reduced neuroendocrine transition of the epithelial tumors. These studies indicate that stable endostatin and angiostatin gene therapy may be more effective for minimally invasive tumors rather than advanced-stage disease. [Cancer Res 2007;67(12):5789–97]
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
Genetic Vectors
Synaptophysin
Angiogenesis Inhibitors
Enzyme-Linked Immunosorbent Assay
Mice, Transgenic
Adenocarcinoma
Metastasis
Adenoviridae
Prostate cancer
Mice
Adjuvant therapy
Medicine
Animals
Angiostatins
Angiostatin
business.industry
Reverse Transcriptase Polymerase Chain Reaction
Prostatic Neoplasms
Genetic Therapy
medicine.disease
Immunohistochemistry
Endostatins
Mice, Inbred C57BL
Disease Models, Animal
Receptors, Vascular Endothelial Growth Factor
Oncology
Tumor progression
Cancer research
Endostatin
business
Tramp
Subjects
Details
- ISSN :
- 00085472
- Volume :
- 67
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....283f35068477a502d7421d5a3de04946